Biological activity of carotenoids: its implications in cancer risk and prevention.

Recently nontoxic natural compounds are getting immense importance for the prevention of diseases of different etiology. Natural product provitamin A "carotenoids", largely α-carotene, ß-carotene, and ß-cryptoxanthin, are typical constituents of orange/red/yellow colored fruits and green vegetables. Different in vitro and in vivo studies have shown that carotenoids possess the capacity to scavenge DNA damaging free radicals, suppress angiogenesis, inhibit cell proliferation and induce apoptosis. Epidemiological reports of case-control studies, nested case-control studies, and cohort studies support significant association between dietary intake and circulating levels of carotenoids and reduction in cancer risk/carcinoma of various organs. However, randomized trials regarding ß-carotene supplementation, alone or in combination with other supplements, have not always well corroborated with this. Of seven trials, one observed a significant benefit on cancer mortality, four reported no significant benefit or harm, while the remaining two trials found an unexpected, but significant increase in lung cancer incidence. This review discusses implications and significance of carotenoids in the field of cancer risk and prevention.

Role of 5-lipoxygenase in resveratrol mediated suppression of 7,12-dimethylbenz(α)anthracene-induced mammary carcinogenesis in rats.

Substantial evidences suggest that lipoxygenase-catalyzed products have a strong influence on the development and progression of human cancers. The dietary phytochemical resveratrol has become a focus of intense research owing to its roles in cancer prevention. A single tail vein injection of 7,12-dimethylbenz(a)anthracene (DMBA) was given at a dose of 0.5mg/0.2 ml oil emulsion/100g body weight at 50 days of age of female Sprague-Dawley rats. Rats were treated with resveratrol from 2 weeks before DMBA injection (5 weeks of animal age) and continued to 24 weeks of the experimentation at a dose of 100 µg/rat in the diet. We observed that resveratrol acts as a potent 5-lipoxygenase (5-LOX) inhibitor obtained from natural sources. Our result indicated that resveratrol is a strong antioxidant in reducing lipid peroxidation and preventing DNA damage. It significantly decreased the extent of DNA strand break, inhibited abnormal cell proliferation as evidenced by BrdU labeling index and also induced apoptosis in carcinogen-challenged rat mammary tissue. Increased TGF-ß1 expression in resveratrol treated rats is thought to be one of the factors inducing apoptosis to suppress DMBA-induced mammary carcinogenesis.

Combined supplementation of vanadium and fish oil suppresses tumor growth, cell proliferation and induces apoptosis in DMBA-induced rat mammary carcinogenesis.

The anti-cancer activity of vanadium and fish oil has been shown in a large number of studies. This study was undertaken to analyze the combined effect of vanadium and fish oil on 7,12-dimethylbenz(α)anthracene (DMBA)-induced mammary carcinogenesis in female Sprague-Dawley rats. The whole experiment was divided into three parts: (1) DNA strand breaks study, (2) morphological analysis, and (3) histological and immunohistochemical study. Rats were treated with DMBA (0.5 mg/0.2 ml corn oil/100 g body weight) by a tail vein injection. Rats received vanadium (w/v) as ammonium monovanadate at a concentration of 0.5 ppm (4.27 µmol/L) in the drinking water and given ad libitum and/or fish oil (0.5 ml/day/rat) by oral gavage. Histology, morphology, DNA strand breaks, cell proliferation, and apoptosis of the mammary tissue were assessed in this study. Treatment with vanadium or fish oil alone significantly reduced the DNA strand breaks, palpable mammary tumors, tumor multiplicity, and cell proliferation but the maximum protection effect was found in the group that received both vanadium and fish oil and the combination treatment offered an additive effect (P < 0.05). Furthermore, vanadium and fish oil significantly increased the TUNEL-positive apoptotic cells (P < 0.05) but the increase was maximal with combination treatment and had an additive effect. These results affirm the benefits of administration of vanadium and fish oil in the prevention of rat mammary carcinogenesis which was associated with reduced DNA strand breaks, palpable mammary tumors and cell proliferation and increased TUNEL-positive apoptotic cells.

Combinatorial effect of fish oil (Maxepa) and 1alpha,25-dihydroxyvitamin D(3) in the chemoprevention of DMBA-induced mammary carcinogenesis in rats.

The present study demonstrates the anti-tumor effects of combined supplementations of dietary fish oil (Maxepa) and 1alpha,25-dihydroxyvitamin D(3) (vitamin D(3)) on 7,12-dimethylbenz(alpha)anthracene (DMBA)-induced rat mammary carcinogenesis. Female Sprague-Dawley rats at 50 days of age were treated with 7,12-dimethylbenz(alpha)anthracene (DMBA; 0.5mg/100g body weight) by a single tail vein injection in an oil emulsion. Both fish oil (rich in EPA and DHA) and vitamin D(3) were administered orally at a dose of 0.5 ml/day/rat and 0.3 microg/100 microL propylene glycol twice a week respectively and continued to 35 weeks after DMBA administration. Fish oil in combination with vitamin D(3) resulted in a significant reduction in incidence, multiplicity and volume of mammary tumors. These supplementation also inhibited DMBA-induced mammary 7-methylguanine DNA adducts formation, which was measured by HPLC-fluorescence assay (at four sequential time points; ANOVA, F=42.56, P<0.0001). Immunohistochemical analysis revealed that the effect of fish oil and vitamin D(3) occurred through suppression of cell proliferation (BrdU-LI: P<0.0001). Fish oil and vitamin D(3) together also reduced the mRNA expression of iNOS (84%, P<0.05). In view of their natural availability, non-toxicity and acceptability; combined supplementation of fish oil and vitamin D(3) might be effective for chemoprevention of mammary carcinogenesis.

Fish oil regulates cell proliferation, protect DNA damages and decrease HER-2/neu and c-Myc protein expression in rat mammary carcinogenesis.

BACKGROUND & AIMS: The aim of this study is to assess the effect of dietary fish oil (MaxEPA) on DNA-strand breaks, cell proliferation and anti-apoptotic protein expressions in rat mammary carcinogenesis. METHODS: Eighty-one female Sprague-Dawley rats were divided into two parts, one for DNA-strand breaks study and the other for immunohistochemical study. Female Sprague-Dawley rats were treated with 7,12-dimethylbenz(alpha)anthracene (DMBA) (0.5 mg/0.2 ml corn oil/100 g body weight) by a tail vein injection. Rats were fed either fish oil or corn oil (0.5 ml/day/rat) by oral gavage. RESULTS: Fish oil-treated group showed significant protection against generation of single-strand breaks (SSBs) (56.1%, P < 0.05) but increased effect (72.3%, P < 0.05) was found in the corn oil-treated group when compared to DMBA control group. Furthermore, fish oil-treated group exhibited substantial decrease in Ki-67 (P < 0.05), HER-2/neu (P < 0.05) and c-Myc (P < 0.05) immunolabelling indices when compared to carcinogen counterpart. However, corn oil treatment resulted in significant increase in the above parameters. CONCLUSIONS: The above data support the role of n-3 PUFA as a preventive agent for DNA damages and a potential to inhibit mammary carcinogenesis.